Sunday, June 4, 2023

Visualising the flow of calcium that makes the heart beat

Catching heartbeat ‘molecular switch’ in action.

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Scientists at Oxford University have devised a new method that uses protein originally found in marine corals to uncover the effects of genetic errors that contribute to a heart condition. The method tracks the flow of calcium in the heart that makes a heartbeat.

Until now, there was no way to track the ebb and flow of calcium to the fibers that respond to calcium for heart contracts. Previously, scientists tried extracting a protein from the Discosoma marine coral and tuned it to glow red in the presence of calcium.

During the study, scientists genetically altered adenovirus to insert this protein into heart muscle fibers taken from guinea pigs. They then used special cameras to track the ebb and flow of the red glow that signaled calcium in action as it made the living muscle fibers contract.

Dr. Matthew Daniels, a researcher at Oxford University’s Radcliffe Department of Medicine said, “The difficult part was trying to find some way of sneaking a peek at calcium at work in a very complicated machine that, like the engine of your car, doesn’t have a lot of room under the bonnet.”

“But it turns out that there is a big enough gap right next to the protein that we measure when a patient comes in with a suspected heart attack. We can get a harmless virus to make that protein, with an added extension which glows red when calcium is nearby.”

The specialists likewise rehashed the experiment with heart muscle fibers that had been adjusted to have genetic errors that outcome in a heart disease known as hypertrophic cardiomyopathy, where heart muscles turn out to be unusually thickened, making each heartbeat stiffer. There are at present no medicines for the progressions that reason this condition.

Scientists found that heart fibers with hypertrophic cardiomyopathy mutations held onto more calcium, for much longer than normal. This explains why cells from hypertrophic cardiomyopathy patients burn through the cells energy stores much more quickly, as they don’t switch off efficiently.

Dr. Daniels said: ‘Our technique found hypertrophic cardiomyopathy works in a very different way from what we’d thought previously.

‘This is because our method really allows us to focus on the actual site where the muscle fibers contract, while avoiding signals from other parts of the cell. It’s a bit like listening to your car engine while sitting inside with the radio on, versus listening to only engine as the fuel ignites to power your car.’

Scientists are now planning to utilize these tools to think about more instances of hypertrophic cardiomyopathy which can be brought about by a different kind of genetic change. In the event that these discoveries apply all the more generally, at that point it is conceivable to utilize these devices to recognize and test new medications in cells in a lab.

The study is published in the journal Circulation Research and was funded by the Wellcome Trust and the British Heart Foundation.

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